Devices and methods for excluding the left atrial appendage

ABSTRACT

Devices and methods for occluding the left atrial appendage (LAA) to prevent blood from clotting within the LAA and subsequently embolizing, particularly in patients with atrial fibrillation. A foam implant encapsulated with a tough thromboresistant membrane is placed via transvascular means into the LAA and anchored with adhesives and/or mechanical anchors. Tissue over- and in-growth are optimized to anchor the implant in place and provide a permanent occlusion.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the priority benefit under 35 U.S.C. § 119(e) ofU.S. Provisional Application No. 61/779,802, filed Mar. 13, 2013, theentirety of which is hereby incorporated by reference herein.

FIELD OF THE INVENTION

The embodiments disclosed herein relate to devices and methods foroccluding the left atrial appendage (LAA) to prevent blood from clottingwithin the LAA and subsequently embolizing, particularly in patientswith atrial fibrillation.

BACKGROUND OF THE INVENTION

Atrial fibrillation (Afib) is a condition in which the normal beating ofthe left atrium (LA) is chaotic and ineffective. The left atrialappendage (LAA) is a blind pouch off the LA. In patients with Afib bloodstagnates in the LAA facilitating clot formation. These clots (or clotfragments) have a tendency to embolize or leave the LAA and enter thesystemic circulation. A stroke occurs when clot/clot fragment embolizesand occludes one of the arteries perfusing the brain. Anticoagulants,e.g. Coumadin, have been shown to significantly reduce the stroke riskin Afib patients. These drugs reduce clot formation but also increasedbleeding complications including hemorrhagic strokes, subdural hematomaand bleeding in the gastrointestinal tract.

There are about 8 million people in the US and EU with Afib. About 4.6million of these patients are at a high risk for stroke and wouldbenefit from anticoagulation. A large portion of these patients cannottake anticoagulants due to an increased bleeding risk leaving theirstroke risk unaddressed. The prevalence of Afib increases with age.

Several devices for occluding the LAA are described in the prior art andeach has limitations this invention improves upon. The prior art devicesare metal structures which are circular in cross section and are made toexpand to fill the LAA ostium. These devices are offered in many sizesand must be closely matched to the highly variable LAA anatomy. This isdifficult to do using fluoroscopy and often requires adjunctive imagingin the form of transesophageal echocardiography, cardiac CT and MRI, allwith three dimensional reconstructions. If the device is significantlyoversized, the LAA ostium may become overstretched leading to tearingresulting in bleeding into the pericardial space. If the device is toosmall, it will not adequately seal the ostium and may be prone toembolization. Even if sized correctly, the device forces the oval LAAostium to take the round shape of the device, often resulting inresidual leakage at the edges due to poor sealing.

Anchoring of these implants in the proper location is described in theprior art devices predominately using an array of radially disposedbarbs or hooks which engage into the surrounding cardiac tissue uponexpansion of the device. The device must therefore have sufficientspring force or stiffness for the barbs to engage the surroundingtissue. These barbs may lead to leaking of blood through the tissue intothe pericardial space which may lead to cardiac tamponade. Furthermore,the geometry of these barbs and hooks prevent additional positioningonce the implant is fully expanded.

For all of these reasons it would be desirable to have a device whichdid not require an excessive number of sizes requiring extensivepre-procedure imaging, could be repositioned when fully expanded andsecured without an array of hooks or barbs.

SUMMARY OF THE INVENTION

Devices and methods for occluding the left atrial appendage (LAA) toprevent blood from clotting within the LAA and subsequently embolizingare disclosed herein. These concepts include the ability to deliver adevice through a catheter that is tracked over a guide wire through thevascular system. Foams are described that are collapsed for delivery andthen expand in place in the LAA. Anchoring of these plugs are made bytissue ingrowth from the LAA into the foams, adhesives, barbs or distalanchoring elements. Foam plugs are described that are encapsulated withjackets that are sufficiently strong to enable handling of the plugswithout tearing and also to encourage the creation of a neointima on atleast the proximal, LA facing side.

There is provided in accordance with one aspect of the presentinvention, a left atrial appendage occlusion device. The devicecomprises an expandable, open cell foam body having a proximal end, adistal end and a side wall. A skin covers at least the proximal (atrial)end of the body, and an expandable lumen extends through the body. Thelumen can support a portion of a delivery catheter and/or a guidewire,but collapses to a near zero cross sectional area when such componentsare removed. This feature reduces the likelihood of emboli formingwithin the central lumen and dislodging into the bloodstream. The bodyis compressible within a delivery catheter having an inside diameter ofno more than about 20 F and can self expand to a diameter of at leastabout 25 mm when released from the delivery catheter.

In one implementation of the invention, the skin comprises ePTFE. Theskin may extend throughout the length of the guidewire lumen, and mayadditionally cover at least a portion of the distal end as well as theproximal end of the body. In one embodiment, the skin comprises atubular ePTFE sleeve, which extends through the guidewire lumen in theopen cell foam body, and everts back over the outside of the body, forconnection to itself to encase the open cell foam body and line theguidewire lumen.

Preferably, at least one tissue ingrowth surface is provided on the sidewall of the body, such as by providing at least one aperture through theskin to place the open cell foam body in direct contact with adjacenttissue. The tissue ingrowth surface may comprise at least about 20%,40%, 60%, 80% or more of the surface area of the side wall of the body.

At least one radiopaque marker may be provided, such as a radiopaquewire or thread, and/or the foam and/or skin can be loaded with orimpregnated with a radiopaque filler such as barium sulfate, bismuthsubcarbonate, or tungsten to permit fluoroscopic visualization. At leastone or two or more tissue penetrating elements or other anchors may beprovided.

In accordance with another aspect of the present invention, there isprovided a left atrial appendage closure system. The system comprises adelivery catheter, comprising an elongate flexible tubular body, havinga proximal end and a distal end and at least one lumen extendingtherethrough. A self-expandable open cell foam body compressed withinthe distal end of the delivery catheter carries a skin covering at leasta portion of the body, and a guidewire extending through the body. Anaxially moveable deployment control such as a push wire extends throughthe lumen, for deploying the foam body from the distal end of theclosure system.

The system may additionally comprise a guidewire, having an inflatableballoon thereon. Preferably, at least one tissue ingrowth area isprovided on the body, such as by exposing the open cell foam bodythrough at least one window in the skin.

BRIEF DESCRIPTION OF THE DRAWINGS

The presently disclosed embodiments will be further explained withreference to the attached drawings, wherein like structures are referredto by like numerals throughout the several views. The drawings shown arenot necessarily to scale, with emphasis instead generally being placedupon illustrating the principles of the presently disclosed embodiments.

FIG. 1 shows the anatomy of the left atrium and left atrial appendage.

FIG. 2 shows a left atrial appendage with one foam plug embodiment inplace that uses adhesive.

FIG. 3 shows an x-ray image of a foam plug.

FIG. 4 shows a left atrial appendage with foam embodiment and distalanchor in place.

FIG. 5 shows a screw anchor.

FIG. 6 shows a longitudinal cross section of a foam plug embodiment.

FIG. 7 shows an LAA cross section.

FIG. 8 is a schematic illustration of a guide catheter approaching theostium to the left atrial appendage.

FIG. 9 is an illustration as in FIG. 8, with a guidewire placed withinthe left atrial appendage.

FIG. 10 is an illustration as in FIG. 9, with an inflatable balloon atthe distal region of the guidewire positioned within the left atrialappendage.

FIG. 11 is an illustration as in FIG. 10, with the guide catheteradvanced distally along the guidewire and into the left atrialappendage.

FIG. 12 is an illustration as in FIG. 11, showing the occlusion deviceand pusher positioned within the guide catheter.

FIG. 13 is an illustration as in FIG. 12, showing the occlusion devicepartially deployed exiting the guide catheter.

FIG. 14 is an illustration as in FIG. 13, with the occlusion devicefully deployed within the left atrial appendage.

FIG. 15 is an illustration as in FIG. 14, showing the deployment ofadhesives or other anchoring structures to retain the occlusion devicewithin the left atrial appendage.

FIG. 16 shows a plug occlusive device in longitudinal cross sectionusing metal and foam.

FIG. 17 shows a plug using metal coils and foam.

FIG. 18 shows a plug using a single metal coil.

FIG. 19 shows a plug with a dilating distal tip.

FIG. 20 shows a plug with proximal and distal caps.

FIG. 21 shows a plug adhesive delivery system.

FIG. 22 shows the delivery of an expanding foam system.

FIG. 23 shows a plug with barbs.

FIG. 24 shows a plug with a retrieval suture attachment.

FIGS. 25A and 25B show a distal anchoring system.

FIG. 26 shows an alternative distal anchoring system.

While the above-identified drawings set forth presently disclosedembodiments, other embodiments are also contemplated, as noted in thediscussion. This disclosure presents illustrative embodiments by way ofrepresentation and not limitation. Numerous other modifications andembodiments can be devised by those skilled in the art which fall withinthe scope and spirit of the principles of the presently disclosedembodiments.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The heart 100 is shown in FIG. 1 with the left atrial appendage (LAA)102 which is a cavity emanating from the left atrium (LA) 104. The LAA102 is quite variable in shape in all dimensions. If the heart is notbeating normally, a condition called atrial fibrillation, blood withinthe LAA becomes stagnant which promotes clot formation. If blood clotswithin the LAA, the clots may pass from the LAA 102 to the LA 104, tothe left ventricle 106 and out of the heart 100 into the aorta. Vesselsthat bring blood to the brain branch off the aorta. If the clot passesto the brain via these vessels, it may get stuck and occlude a smallvessel in the brain which then causes an ischemic stroke. Strokes havesevere morbidities associated with them.

The opening of the LAA 102 to the LA 104 is called an ostium 110. Theobject of this invention is to occlude the ostium 110 thereby sealingoff the LA 104 from the LAA 102. The ostium 110, is oval, highlyvariable and dependent of loading conditions, i.e., left atrialpressure.

One embodiment of the LAA occlusion device is shown in FIG. 2. Theocclusion device or plug 204 is placed within the LAA 200 at its openingto the LA 202. The plug 204 comprises an expandable media such as anopen cell foam which enables collapse and expansion of the plug and alsoto enhance ingrowth of tissue into the foam. The foam plug 204 is atleast partially encapsulated within a thin strong layer 206 such asePTFE (expanded polytetrafluoroethylene), polyolefin or polyester.Alternatively bioabsorbable materials could be utilized such as PLA,PGA, PCL, PHA, or collagen. This thin encapsulating layer can beoriented or otherwise modified to be elastomeric in at least onedirection, such as radially.

The plug may be made of polyurethane, polyolefin, PVA, collagen foams orblends thereof. One suitable material is a polycarbonate-polyurethaneurea foam with a pore size of 100-250 um and 90-95% void content. Thefoam could be non-degradable or use a degradable material such as PLA,PGA, PCL, PHA, and/or collagen. If degradable, the tissue from the LAAwill grow into the foam plug and replace the foam over time. The plug204 may be cylindrical in shape in an unconstrained expansion but mayalso be conical with its distal end smaller than the proximal end orreversed. It could also be oval in cross section to better match theopening of the LAA.

The foam plug 204 is oversized radially in an unconstrained expansion tofit snuggly into the LAA and may be 5-50 mm in diameter depending on thediameter of the target LAA. The length of the plug is similar to orgreater than its diameter such that the L/D ratio is about or greaterthan about 1.0 or greater than about 1.5 or greater than about 2.0 tomaximize its stability. The compliance of the material is designed suchthat it pushes on the walls of the LAA with sufficient force to maintainthe plug in place but without overly stretching the LAA wall. The foamand/or skin also conforms to the irregular surfaces of the LAA as itexpands, to provide a complementary surface structure to the native LAAwall to further enhance anchoring and promote sealing. Thus, while someleft atrial appendage occlusion devices in the prior art include amechanical frame which forces at least some aspect of the left atrialappendage into a circular configuration, the expandable foam implant ofthe present invention conforms to the native configuration of the leftatrial appendage. In one embodiment, the structure of the foam may befabricated such that squeezing axially on the opposing ends of the foamcauses the foam to increase in diameter.

The ePTFE or foam material may be provided with one or two or moreradiopaque markers such as radiopaque threads 210 or be filled with orimpregnated with a radiopaque filler such as barium sulfate, bismuthsubcarbonate, or tungsten which permit the operator to see under x-raythe plug for proper positioning in the anatomy. An x-ray image is shownin FIG. 3 where one cannot see the foam plug 300 but can clearly see thethreads 302 and the crimp 304 (discussed below). This thread or ribbonmay be made from a radiopaque metallic wire such as platinum or tungstenor a polymer with a radiopaque filler such as barium, bismuth, tantalum,tungsten, titanium or platinum.

The outer ePTFE layer may be formed from a tube with a diameter aboutthe same diameter of the foam plug and a wall thickness between about0.0001″ and about 0.001″ thick and serves to allow one to collapse andpull on the plug without tearing the foam material. The ePTFE materialalso serves as the blood contacting surface facing the left atrium 206and has pores or nodes such that blood components coagulate on thesurface and an intimal or neointimal covering of tissue grows across itand anchors tightly to the material. Pore sizes within the range of fromabout 4μ to about 110μ, ideally 5-35μ are useful for formation andadherence of a neointima.

The outer covering 206 may be constructed of materials other than ePTFEsuch as woven fabrics, meshes or perforated films made of FEP,polypropylene, polyethylene, polyester or nylon. The covering shouldhave a low compliance (non-elastic), at least longitudinally, besufficiently strong as to permit removal of the plug, a low coefficientof friction, and be thromboresistant. The outer covering serves as amatrix to permit plug removal as most foams are not sufficiently strongto resist tearing when pulled. The plug can also be coated with orcontain materials to enhance its ultrasonic echogenic profile,thromboresistance, lubricity, and/or to facilitate echocardiographicvisualization, promote cellular ingrowth and coverage.

The outer covering has holes in it to permit contact of the LAA tissuewith the foam plug to encourage ingrowth of tissue into the foam plugpores. These holes may be 1 to 5 mm in diameter or may also be oval withtheir long axis aligned with the axis of the foam plug, the length ofwhich may be 80% of the length of the foam plug and the width may be 1-5mm. The holes may be as large as possible such that the outer coveringmaintains sufficient strength to transmit the tensile forces requiredfor removal. The holes may be preferentially placed along the device. Inone embodiment, holes are placed distally to enhance tissue ingrowthfrom the LAA wall.

In one implementation of the invention, the implant is provided withproximal and distal end caps of ePTFE, joined together by two or threeor four or more axially extending strips of ePTFE. The axially extendingstrips are spaced apart from each other circumferentially, to provide atleast two or three or four or more laterally facing windows throughwhich the open cell foam body will be in direct contact with the tissuewall of the left atrial appendage. This outer covering could be a meshor netting as well. As shown in FIG. 20, the covering 2004 is only onthe proximal and distal faces of the plug 2000. They may be glued to thefoam plug and then crimped to the center tube 2002.

One means of adhering the foam plug in place within the LAA is to use anadhesive, such as a low viscosity cyanoacrylate (1-200 cps). Theadhesive is injected into place along the sidewall near the distal endof the foam plug 208. Holes in the ePTFE covering permit the adhesive tointeract between the foam plug 204 and the LAA wall 200. Injection ofthe adhesive may be accomplished with several means, one of which is toinject through the catheter into the center lumen 212. Passages 214serve to guide the adhesive to the correct location. The distal end ofthe foam plug must be restricted at that time to prevent the adhesivefrom exiting the distal crimp 216. Alternatively, FIG. 21 shows tubes2104 that are pre-placed through the guide catheter 2102, through thecenter lumen of the plug 2106 and bend backwards in the LAA to thedistal end of the plug 2100. These tubes 2104 pass all the way to theproximal end of the guide catheter 2102 where a fitting is attached topermit injection of the adhesive which then exits the small tubes 2104at the desired location of the plug. These tubes are made ofpolyethylene, polypropylene or FEP so that the adhesive will not adhereto the tubes. The tubes 2104 are withdrawn after injection through theguide catheter out of the patient.

Other one part adhesives including aqueous cross linking adhesives,polyurethane, PEG, PGA, PLA, polycaprolactone or a lycine-derivedurethane may be used. In addition, these adhesives may be made in twocomponents such that one component is adherent to the foam and thesecond injected in vivo. Also, these two component adhesives may beinjected simultaneously to mix in vivo to prevent fouling of injectiontubes.

An alternative anchoring means for plug 400 is one or two or more distalanchors as shown in FIG. 4. Wire 404 is passed through the center lumen410 into the LAA and attached to the distal wall of the LAA. In thiscase, a screw wire 408 is threaded into the wall of the LAA 406. Acloser detail of this is seen in FIG. 5 as screw 502 is shown embeddedinto the LAA wall 504 but not all the way through the epicardial surface506.

Additional means of anchoring include the use of a plurality of hooks orbarbs or graspers to grab the distal wall and baskets, mallecots, distalfoam plugs and Nitinol wire birds nests that open within the LAA andpush outward on the wall or engage the protrusions of the LAA. It may bedesirable to place the plug then engage the anchor as a secondary step.One such embodiment could include a multitude of nitinol wires with aball or catch welded proximal to the anchor tip. These could be gatheredwith the delivery catheter then released when the ideal plug positionhas been confirmed.

A cross section of one embodiment is shown in FIG. 6 with foam plug 600and the left atrium face 602 and the LAA face 610. The ePTFE material604 encapsulates the foam plug 600 and its open ends are connected withan attachment structure such as a wire, suture or tubular crimp 606 overan inner tube 608. The inner tube 608 may be made of an implant gradestainless steel such as 304 or 316 grades or a cobalt-chromium alloysuch as MP35n and the crimp 606 may be made of annealed 304 or 316stainless steel or a cobalt-chromium alloy such as MP35n. This crimpalso serves as an element which can be snared should the device need tobe removed.

Referring to FIG. 6, the tubular ePTFE layer 604 extends along an innerlayer 612 which lines the guidewire lumen, and everts out around theleft atrial face 602 to form outer layer 614. A first end 616 of innerlayer 612 is disposed concentrically within a second end 618 of outerlayer 614. The first end 616 and second end 618 are clamped betweeninner tube 608 and outer crimp 606. In this manner, the implant can beencapsulated in a manner that presents a seamless left atrial face 602,and preserves the integrity of the guidewire lumen with inner tube 608.

Placement of the device is shown in FIG. 7 through 15. To close the leftatrial appendage, the left atrium (LA) must first be accessed from thevenous system. One approach is to use a Brockenbrough-style needle topuncture the atrial septum to access the LA from the right atrium (RA).The basic needle-puncture technique is performed obtaining venous accesstypically via the right femoral vein. A Mullins sheath and dilator arethen tracked over a 0.025″ or 0.032″ guide wire previously placed in thesuperior vena cava (SVC). Fluoroscopic and echocardiographic imaging,such as transesophageal echo (TEE) or intracardiac echo (ICE), aretypically utilized. If echo is not utilized, it is common to also placea pigtail catheter in the aortic root to define the location of theaortic valve, a step not necessary when using echo.

Once the Mullins sheath and dilator are in the SVC, the guide wire isremoved and a trans-septal needle is placed through the dilator. Theneedle contains a stylette to prevent skiving off of polymeric materialfrom the dilator lumen as it traverses to the tip. Once the needle isnear the dilator tip, the stylette is removed and the needle isconnected to a manifold and flushed. The Mullins sheath/dilator set andthe needle (positioned within the dilator tip) are retracted into theSVC toward the RA as a unit. As the system is withdrawn down the wall ofthe SVC into the RA and positioned in the fossa ovale, the preferredpuncture location.

Once proper position in the fossa ovale is observed, the needle isadvanced across the fossa ovale into the LA. Successful trans-septalpuncture can be confirmed by echo, pressure measurement, O₂ saturationand contrast injection. Once the needle position is confirmed to bepositioned in the LA, the sheath and dilator can be advanced over itinto the LA. In some cases, the user will first pass a guide wirethrough the needle into the LA and into an upper pulmonary vein(typically the left) prior to crossing. Alternative options include theuse of radiofrequency trans-septal needles, which are useful forcrossing very thick or hypertrophic septa, or the use of a safety wireplaced through the needle and utilized for the initial puncture.

Referring to FIGS. 8 through 15, a guide catheter 802 is placed throughthe femoral vein into the right atrium of the heart and across theintra-atrial septum into the left atrium as described above andpositioned near the LAA ostium 804. A guidewire 902 usually of 0.035″diameter is placed through guide catheter 900 and into the LAA 904. Thisguidewire 1002 may have attached to its distal end a balloon 1006 whichis inflated in the LAA and serves as a bumper to prevent guide catheter1100 from perforating the wall of the LAA. The guide catheter 1100 isthen advanced over the guide wire 1108 into the LAA 1104. A radiopaquemarker 1102 is used to guide catheter placement under fluoroscopy. Thefoam plug 1204 is then pushed through the guide catheter 1200 withpusher 1202 and is shown exiting the guide catheter 1300 slowly in FIG.13 until it is fully deployed as shown in FIG. 14. The foam plug 1404position may then be adjusted in place using the distal balloon 1408 andthe guide catheter 1400, sliding the foam plug proximally by pulling onthe balloon 1408 through shaft 1412 or sliding it distally by pushingguide catheter 1400 distally. The guide wire may also contain a pressuresensor within it such that sealing of the LAA is monitored andconfirmation of a sufficient seal is made. Once the user is happy withthe placement, the adhesive 1514 may be injected and/or mechanicalanchors be deployed anchoring the plug to the wall. The guide wireballoon 1508 is deflated, after which the guide wire. In an alternativeembodiment, a binary adhesive system can be used where one component ofthe binary system is bonded to the outer surface of the skin coveringthe foam plug. The second component can be injected at the interfacebetween foam plug and the wall of the LAA such that bonding happens onlyat the interface minimizing the risk of adhesive embolization.

An alternative to pushing the plug through the entire length of theguide catheter is that the plug 1204 may be initially located at thedistal end of the guide catheter 1200 as shown in FIG. 12. The guidewire1210 passes through the center of the plug 1204 and in this mode, thepusher 1202 only needs to push the plug a short ways to deploy it intothe LAA.

For alternative anchors, they may be deployed, the shafts disconnectedand removed. Disconnection mechanisms may be any of several types, suchas threaded, electrolytic detachment, or others known in the art.

Alternative plug concepts include a combination of foam and metalimplant as shown in FIG. 16. The foam 1600 is designed to provideingrowth of tissue and also to provide a cushion of the metal stent 1602onto the tissue of the LAA. The proximal face of the plug is covered inePTFE, polyester or another thromboresistant tissue scaffold material tofacilitate sealing with the desired pore size to encourage overgrowth.Stent 1602 could be made of Nitinol to enable it to pack into a 10, 12,14, 16, 18 or 20 F delivery catheter and expand to its desired diameter.It could be braided, laser cut or wire formed. Any of a variety of stentwall patterns may be utilized, depending upon the desired performance.The stent may be a balloon expandable stent, or self-expandable stent asare understood in the art. In the illustrated embodiment, aself-expandable stent 1602 comprises a plurality of proximal apexes 1608and distal apexes 1610 connected by a plurality of zig zag struts 1612.A hole 1606 allows passage of the guidewire for delivery. This designmay be advantageous in that the expansion force exerted by the plug onthe LAA can be controlled separately from the foam characteristics.Also, it may be easier to pack this concept into a smaller geometry.

Alternatively, the foam plug may be constructed of 2 foams. One densercore to provide force and an outer softer foam to engage the tissueirregularities. The softer foam could also be located on the proximaland/or distal ends to facilitate retrieval.

Another means of adding stiffness to the foam plug is shown in FIG. 17where a cavity 1704 in the foam plug 1700 is made and a coil of wire1702 may be advanced from the guide catheter at the proximal end 1706into the cavity 1704. As the wire enters the cavity, it expands to itspredetermined size and exerts force on the foam radially outwards. Thetype and amount of wire may be determined in vivo using x-ray guidanceto examine the radial expansion of the foam into the LAA.

Instead of wires as shown in FIG. 17, a balloon may be passed into thefoam and inflated to provide radial force while the outer foam serves toengage the tissue irregularities and tissue ingrowth. Followinginflation, the balloon may be detached from a deployment catheter andthe deployment catheter withdrawn. The balloon is preferably providedwith a valve, to prevent the escape of inflation media. Inflation mediamay be any of a variety of media which is convertible between a first,flowable state and a second, hardened state such as by cross linking orpolymerization in situ.

Another LAA plug is shown in FIG. 18 as a spring like implant wire 1800that is covered with foam 1802 to encourage ingrowth. The proximal faceof the implant is covered with a sheet of ePTFE or other tissuescaffolding material. This implant may be stretched out for delivery andreleased in place.

Rather than using a foam, a low porosity outer bag without perforationscould be placed in the LAA and then filled with a substance to providethe radial expansion. This substance may be a hydrogel, cellulose orpolyvinylacetate.

Rather than requiring the use of a separate dilation device to cross theseptum, the distal crimp element 1902 may be formed in a tapered mannersuch that it extends from the distal end of the catheter 1200 and servesas a dilating tip to dilate the opening in the septum as the catheter isadvanced. See FIG. 19.

An alternative plug design uses a foam such as cellulose sponge materialthat is compacted and dehydrated such that it can be packed into theguide catheter. This foam material 2202 may be packed into the guidecatheter as shown in FIG. 22. The foam plug 2202 is then advanced fromthe distal end of the guide catheter 2204 with a plunger 2206 into theLAA. The plug exits the guide catheter and opens to a disc shape 2210.As the foam absorbs fluid in the blood, its length expands to form acylinder 2220 filling the LAA. Expansion ratios for compressed cellulosematerials may be as high as 17:1, expanded to compressed length.

It may be advantageous to use small barbs 2302 in FIG. 23 to furtherengage the plug 2204 into the LAA. Barbs may be unidirectional orbidirectional to resist movement in either the proximal or distaldirection. These barbs are embedded into the foam plug and may be 0.1 to1 mm in height. It may be desirable to place the plug then engage thebarbs as a secondary step. One such embodiment could include a multitudeof nitinol barb wires with a ball or catch welded proximal to the barbtip. These could be gathered with the delivery catheter within a sleeveor suture then released when the ideal plug position has been confirmed.

One means of removing a device that is not functioning properly is toreleasably attach a retrieval suture 2400 to the implant, such as to theproximal cap 2402 which also passes proximally throughout the entirelength of the guide catheter 2404 in FIG. 24. If the device is to beremoved, pulling on both ends of the suture 2400 will pull the outercovering into the guide catheter 2404 which can then be removed from thepatient. If the device is properly placed, the suture 2400 may be cutand removed leaving the plug in place.

Deployment of the occlusion device has been discussed primarily in thecontext of a transvascular access. However, implants of the presentinvention may alternatively be deployed via direct surgical access, orvarious minimally invasive access pathways (e.g. jugular vein). Forexample, the area overlying the xiphoid and adjacent costal cartilagemay be prepared and draped using standard techniques. A local anestheticmay be administered and skin incision may made, typically about 2 cm inlength. The percutaneous penetration passes beneath the costalcartilage, and a sheath may be introduced into the pericardial space.The pericardial space may be irrigated with saline, preferably with asaline-lidocaine solution to provide additional anesthesia and reducethe risk of irritating the heart. The occlusion device may thereafter beintroduced through the sheath, and through an access pathway createdthrough the wall of the LAA. Closure of the wall and access pathway maythereafter be accomplished using techniques understood in the art.

Depending upon the desired clinical performance, any of the LAAocclusion devices of the present invention may be provided with a drugor other bioactive agent, which may be injected via the deploymentcatheter, or impregnated within the open cell foam or coated on theimplant. The bioactive agent may be eluted or otherwise released fromthe implant into the adjacent tissue over a delivery time periodappropriate for the particular agent as is understood in the art.

Useful bioactive agents can include those that modulate thrombosis,those that encourage cellular ingrowth, throughgrowth, andendothelialization, and potentially those that resist infection. Forexample, agents that may promote endothelial, smooth muscle, fibroblast,and/or other cellular growth into the implant including collagen (Type Ior II), heparin, a combination of collagen and heparin, extracellularmatrix (ECM), fibronectin, laminin, vitronectin, peptides or otherbiological molecules that serve as chemoattractants, molecules MCP-1,VEGF, FGF-2 and TGF-beta, recombinant human growth factors, and/orplasma treatment with various gases.

Anti-thrombotics can typically be separated into anti-coagulants andanti-patelet agents. Anti-Coagulants include inhibitors of factor(s)within the coagulation cascade an include heparin, heparin fragments andfractions as well as inhibitors of thrombin including hirudin, hirudinderivatives, dabigatran, argatroban and bivalrudin and Factor Xinhibitors such as low molecular weight heparin, rivaroxaban, apixaban.

Antiplatelet agents include GP 2b/3a inhibitors such as epifibitide, andabciximab, ADP Receptor agonists (P2/Y12) including thienopyridines suchas ticlopidine, clopidogrel, prasugrel and tacagrelor and aspirin. Otheragents include lytic agents, including urokinase and streptokinase,their homologs, analogs, fragments, derivatives and pharmaceutical saltsthereof and prostaglandin inhibitors.

Antibiotic agents can include, but are not limited to penicillins,cephalosportins, vancomycins, aminoglycosides, quinolonges, polymyxins,erythromycins, tetracyclines, chloraphenicols, clindamycins,lincomycins, sulfonamides, their homologs, analogs, derivatives,pharmaceutical salts and combinations thereof.

Another means of anchoring is shown in FIG. 25A where the foam plug 2500is placed in the LAA. The distal screw lead 2502 is advanced and screwedinto the LAA wall. Guide 2506 is pulled proximally as shown in FIG. 25B.When this guide 2506 is pulled back, the screw lead wire, made ofNitinol, bunches up into a “birds nest” 2508 or forms a coil inside thefoam plug 2500. The screw lead wire 2502 is pushed distally from theguide catheter 2504 with a pusher 2510 and continues to bunch up intothe foam. The catheter system 2504, 2506 and 2510 are then removed.

Another means of anchoring the distal anchor element to the foam isshown in FIG. 26. Two barbed leads 2604 are attached to anchor 2602 suchthat when advanced into place in the foam plug 2600, the barbs 2604 diginto the foam plug.

Biologic agents as outlined above maybe be added to the implant 204 andmay be injected through the delivery catheter into the space between theproximal cap 206 and the foam plug 204. This may serve as a reservoir tominimize thrombus formation during the initial implantation and reducethe need for systemic anticoagulation following device implantation.

An electronic pressure sensor may be embedded into the proximal end ofthe foam plug which may be used to transmit LA pressure to a remotereceiver outside the body for the monitoring of LA pressure which isuseful to monitor cardiac function. In addition, a cardiac pacer ordefibrillator may be embedded into the foam plug and attachedelectrically to the distal anchor. A drug delivery reservoir may beembedded with connection to the LA for controlled delivery of biologicagents as outlined above.

All patents, patent applications, and published references cited hereinare hereby incorporated by reference in their entirety. It should beemphasized that the above-described embodiments of the presentdisclosure are merely possible examples of implementations, merely setforth for a clear understanding of the principles of the disclosure.Many variations and modifications may be made to the above-describedembodiment(s) without departing substantially from the spirit andprinciples of the disclosure. It will be appreciated that several of theabove-disclosed and other features and functions, or alternativesthereof, may be desirably combined into many other different systems orapplications. All such modifications and variations are intended to beincluded herein within the scope of this disclosure, as fall within thescope of the appended claims.

What is claimed is:
 1. A left atrial appendage occlusion device,comprising: an expandable, open cell foam body having a proximal end forfacing the left atrium following implantation in the left atrialappendage, a distal end for facing into the left atrial appendagefollowing implantation, and a side wall; a guidewire lumen extendingthrough the foam body; a layer having an inner portion extending fromwithin the guidewire lumen and an outer portion everting out around theproximal end of the foam body to form a seamless proximal face forfacing the left atrium and continuing over an outer side of the sidewall and at least partially over the distal end of the foam body, with afirst end of the inner portion of the layer disposed distally of thedistal end of the foam body and concentrically within a second end ofthe outer portion of the layer, with the first end and the second endconnected together with an attachment structure; wherein the foam bodycan be compressed within a delivery catheter having an inside diameterof no more than about 20F and can self-expand to a diameter of at leastabout 25 mm when released from the delivery catheter; and wherein theouter portion of the layer has at least one opening to permit contact ofleft atrial appendage tissue with the foam body to permit tissueingrowth into the foam body.
 2. A left atrial appendage occlusion deviceas in claim 1, wherein the layer comprises ePTFE.
 3. A left atrialappendage occlusion device as in claim 1, comprising at least one tissueingrowth surface on the side wall of the foam body.
 4. A left atrialappendage occlusion device as in claim 3, wherein the tissue ingrowthsurface comprises an exposed surface of the foam body which is notcovered by the layer.
 5. A left atrial appendage occlusion device as inclaim 4, wherein the tissue ingrowth surface comprises at least about20% of the surface area of the side wall of the foam body.
 6. A leftatrial appendage occlusion device as in claim 1, wherein the layercomprises a tubular sleeve and the first end and second end areconnected to each other to enclose the foam body.
 7. A left atrialappendage occlusion device as in claim 6, comprising a plurality ofopenings in the layer to permit tissue ingrowth into the foam body.
 8. Aleft atrial appendage occlusion device as in claim 1, wherein the firstend and second end are connected to each other by a crimp.
 9. A leftatrial appendage occlusion device as in claim 1, further comprising atleast one radiopaque marker.
 10. A left atrial appendage occlusiondevice as in claim 9, wherein the radiopaque marker comprises aradiopaque thread.
 11. A left atrial appendage occlusion device as inclaim 1, wherein the device comprises a substantially cylindricalconfiguration in an unconstrained expansion.
 12. A left atrial appendageocclusion device as in claim 1, further comprising at least one anchor.13. A left atrial appendage occlusion device as in claim 12, wherein theanchor comprises a tissue penetrating element.
 14. A left atrialappendage occlusion device as in claim 13, wherein the tissuepenetrating element comprises a helical wire.
 15. A left atrialappendage closure system, comprising: a delivery catheter comprising anelongate flexible tubular body, having a proximal end and a distal endand at least one lumen extending therethrough; a left atrial appendageocclusion device compressed within the distal end of the deliverycatheter; an axially movable deployment control extending through thelumen, for deploying the left atrial appendage occlusion device from thedistal end of the delivery catheter; and wherein the left atrialappendage occlusion device comprises: an expandable, open cell foam bodyhaving a proximal end for facing the left atrium following implantationin the left atrial appendage, a distal end for facing into the leftatrial appendage following implantation, and a side wall; a guidewirelumen extending through the foam body; a layer having an inner portionextending from within the guidewire lumen and an outer portion evertingout around the proximal end of the foam body to form a seamless proximalface for facing the left atrium and continuing over an outer side of theside wall and at least partially over the distal end of the foam body,with a first end of the inner portion of the layer disposed distally ofthe distal end of the foam body and concentrically within a second endof the outer portion of the layer, with the first end and the second endconnected together with an attachment structure; wherein the foam bodycan be compressed within the delivery catheter which has an insidediameter of no more than about 20F, and wherein the foam body canself-expand to a diameter of at least about 25 mm when released from thedelivery catheter; and wherein the outer portion of the layer has atleast one opening to permit contact of left atrial appendage tissue withthe foam body to permit tissue ingrowth into the foam body.
 16. A leftatrial appendage closure system as in claim 15, further comprising aguidewire, wherein the guidewire has an inflatable balloon thereon. 17.A left atrial appendage closure system as in claim 15, additionallywherein the layer comprises a skin covering at least a portion of thefoam body.